Among women with a BRCA1 or BRCA2 mutation, the reduced risk of breast cancer that results from surgical removal of the ovaries is sustained even if these women take short-term hormone replacement therapy, according to a study published in the Journal of Clinical Oncology .

Inherited mutations in two genes-BRCA1 and BRCA2-have been found to greatly increase the lifetime risk of developing breast and ovarian cancer. Alterations in these genes can be passed down through either the mother’s or father’s side of the family.

Among women with BRCA1 or BRCA2 mutations, risk of breast and ovarian cancer can be reduced by prophylactic (preventive) surgery to remove the ovaries and/or breasts. Bilateral prophylactic oophorectomy (BPO) is the surgical removal of the ovaries before a woman develops ovarian cancer. In addition to reducing the risk of ovarian cancer, BPO also reduces the risk of breast cancer since some breast cancers depend on hormones produced by the ovaries in order to grow.

After the ovaries are removed, women may experience menopausal symptoms such as hot flashes. These symptoms are often more severe in women who have their ovaries removed surgically than in women who reach menopause naturally. Hormone replacement therapy (estrogen with or without progestin) provides effective relief of several of these symptoms, but there is little information about the effect of hormone use in women with BRCA1 or BRCA2 mutations. Of particular concern is whether use of hormone replacement therapy increases the risk of breast cancer in these women.

In order to evaluate whether short-term hormone replacement therapy alters breast cancer risk in women who undergo BPO, researchers evaluated 462 women from North America and Europe who were known to have a BRCA1 or BRCA2 mutation. One hundred and fifty-five of these women had undergone BPO and 307 had not. Hormone replacement therapy was reported by 93 of the 155 BPO patients (60%) and 21 of the 307 non-BPO patients (7%). During the 3.6 years of follow-up, breast cancer was diagnosed in 12 (8%) of the BPO patients and 65 (21%) of the non-BPO patients.

As expected, women who had undergone BPO had a reduced risk of breast cancer. After accounting for factors such as age and parity, risk of breast cancer was reduced by 60% following oophorectomy. The extent of the risk reduction was not influenced by whether or not a woman took short-term hormone replacement therapy, suggesting that hormone replacement therapy does not eliminate the protective effect of BPO on risk of breast cancer.

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The researchers conclude that “women with BRCA1/2 mutations should be discouraged from deferring BPO because of fear of symptoms related to surgical menopause and should be reassured that use of short-term hormone replacement, if needed to manage menopausal symptoms, does not negate the breast cancer risk reduction from BPO.”

An accompanying editorial notes that these findings may “lessen the bitterness” of prophylactic oophorectomy.

Reference: Rebbeck TR, Friebel T, Wagner T et al. Effect of Short-Term Hormone Replacement Therapy on Breast Cancer Risk Reduction After Bilateral Prophylactic Oophorectomy in BRCA1 and BRCA2 Mutation Carriers: The PROSE Study Group. Journal of Clinical Oncology. 2005;23:7804-7810.

Accompanying Editorial: Rubinstein WS. Surgical Management of BRCA1 and BRCA2 Carriers: Bitter Choices Slightly Sweetened. Journal of Clinical Oncology. 2005;23:7772-7774.

Related News:US Task Force Issues Recommendations on BRCA1/2 Testing, Prophylactic Removal of Ovaries and Quality of Life in High-Risk Patients

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